The inaugural Notch Signaling in Development, Regeneration & Disease meeting, to be held August 12-17, 2012 at Bates College, Maine, will address an unmet need in the American scientific community, both academic and industrial. The broad and long-term goal of this conference is to enhance cross-disciplinary discussions and collaborations in this rapidly expanding field and to better address the myriad of mechanistic, developmental, organismal, clinical and therapeutic challenges met by practitioners in the field. The Notch signaling pathway is a central mediator of short-range inter-cellular communication in metazoans, under study since 1914 in Drosophila, in other model organisms since the 1980's, and in human health since 1991. Today it is confirmed that alterations in Notch activity underlie several developmental syndromes (Alagille, Spondylocostal Dysostosis, aortic valve disease), adult onset diseases (CADASIL, various heart and valve malformations, muscular dystrophy, multiple sclerosis) and cause or contribute to cancer initiation, promotion or progression in a tissue-dependent manner. These pathologies reflect both loss of function (e.g., Alagille, CADASIL) and gain of function (e.g., cancer). Because the Notch signaling pathway is unique in its reliance on proteases, in the paucity of signal modulators, and because it is repeatedly used in many organs throughout adult life, the road to chronic management of Notch signaling in disease is obscured by many untoward outcomes with available therapies. The main strategy currently practiced in anti-tumor campaigns is based on g-secretase inhibitors or antagonistic antibodies; however, due to their indiscriminate inhibition of Notch receptors in all organs these reagents proved to be toxic during chronic administration. Expanding the interest in this pathway beyond developmental biology and cancer prevention is the realization that a great hurdle in Alzheimer's disease research is the difficulty in developing reliable Notch-sparing g-secretase inhibitors capable of inhibiting APP cleavage. Solving these puzzles requires outside the box thinking. The Specific Aims for this interdisciplinary yet pathway-focused meeting is to bring together a diverse community of 150 scientists working in every model organism and on nearly every organ system from academia, biotech and the pharmaceutical industry. The participants represent diverse approaches to study Notch function in development, its biochemistry and genetics; this will further facilitate discovery and drug development efforts. The 40 speakers represent world leaders with vast institutional memory as well as late-breaking presentations. Significantly, the informal and confidential environment in Gordon conferences, and the time provided for informal interactions, will create a forum in which cutting edge technologies, ideas and discoveries can be freely exchanged, stimulating new ideas. Most importantly, GRC excels in integrating students, postdocs and investigators wishing to enter a new field, such as the study of this important signaling pathway. PUBLIC HEALTH RELEVANCE: The goal of the proposed Gordon Research Conference on Notch signaling in development, regeneration and disease is to provide a stimulating, international and cross disciplinary forum for the dissemination and discussion of new research, concepts and therapeutic opportunities at the forefront of Notch related biology. Alteration in Notch activity underlies or contributes to a growing list of developmental syndromes (Alagille, Spondylocostal Dysostosis, aortic valve disease), adult onset diseases (CADASIL, Alzheimer's disease, various heart and valve malformations, muscular dystrophy, multiple sclerosis) and cancers, expanding the interest in this pathway well beyond scientists interested in developmental and cell biology to those interested in stem cells, cancer biology and therapy. The meeting will bring together a diverse community of scientists working in every model organism and on nearly every organ system from academia, biotech and the pharmaceutical industry.